NCT03541928 · The Methodist Hospital Research Institute
Phase II High Risk Prostate Cancer Trial Using Gene & Androgen Deprivation Therapies, Radiotherapy, & Surgery
What this study is about
This is a forward-looking phase II study to assess the effectiveness and toxicity of HSV-tk+ valacyclovir gene therapy in combination with androgen deprivation therapy, brachytherapy, external beam radiotherapy, and prostatectomy in previously untreated high-risk prostate cancer.
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This is a prospective phase II study to assess the efficacy and toxicity of HSV-tk+ valacyclovir gene therapy in combination with androgen deprivation therapy, brachytherapy, external beam radiotherapy, and prostatectomy in previously untreated high-risk prostate cancer.
Interventions
DRUG
HSV-Tk
Injection of the HSV-tk gene therapy product in four quadrants of prostate to enhance the immune system via "bystander effect" in which cytotoxicity is conferred to non-transduced neighboring cells. In vivo bystander effects are likely due to a combination of host immunological responses and to gap junction-mediated transport of phosphorylated prodrug metabolites to surrounding cells.
DRUG
Valacyclovir
The recommended dose for this trial is 2 g orally t.i.d. for 14 days (day 1 to day 15 and days 31 to 45). This dose has been calculated to give a similar AUC as 10 mg/kg of intravenous acyclovir administered every 8 hours. This is the same dose regimen used in a previous phase I clinical trial of ADV/HSV-tk plus acyclovir and topotecan in patients with recurrent ovarian cancer.
DRUG
Bicalutamide
The recommended dose for Bicalutamide therapy in combination with an LHRH analogue is one 50 mg tablet once daily (morning or evening), with or without food. It is recommended that Bicalutamide be taken at the same time each day. The use of an oral antiandrogen with medical castration for the treatment of prostate cancer is referred to as combined androgen blockade (CAB). Compared with LHRH-agonist monotherapy, CAB with bicalutamide did not reduce overall QoL but provided an early improvement in QoL related to lower urinary tract symptoms and pain.
DRUG
Leuprolide Acetate
Leuprolide acetate 7.5 mg depot injection will be injected monthly for a total of 2 months.
RADIATION
Brachytherapy, External beam radiotherapy
On day 60, patient will undergo high dose rate (HDR) Brachytherapy. The patient will have 8-14 needle catheters inserted under ultrasound guidance. CT simulation and radiation treatment planning will be performed. The needle catheters will be connected to an HDR afterloader containing an Iridium 192 source. A single dose of 1250cGy will be delivered.
PROCEDURE
Radical prostatectomy
approximately 2-3 weeks after radiotherapy completion, patient will undergo radical retropubic prostatectomy. Use of laparoscopy or robotic assistance will be at the urologist's discretion. Lymph node dissection will be performed.
Primary outcome measures
Biochemical control rate
Time frame: 5-year biochemical disease free survival rate
measured by PSA
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- All patients must have biopsy proven adenocarcinoma of the prostate
- Patients in should have at least one or more of the following characteristics PSA\>20, Gleason score 8-10, Primary Gleason pattern 5, \>4 cores with Gleason 8-10, and Clinical stage T3a-T4.
- No prior surgical, hormonal, or radiotherapy prostate treatment.
- ECOG performance status 0-1
- No evidence of metastatic disease or other malignancy (except squamous or basal cell skin cancers.
- Patients must have PSA within 3 months of entry.
- Signed informed consent to participate in the study must be obtained from patients after they have been fully informed of the nature and potential risks of the study by the investigator (or his/her designee) with the aid of written information.
- Willing to provide biopsies as required by the study.
- Patients must have adequate baseline organ function as assessed by the following laboratory values before initiating the protocol:
- serum creatinine \< 1.5 mg%
- T. bilirubin \< 2.5 mg%, ALT and AST \< 2x normal
- Pts \> 100,000/mm3 , ANC\> 1500 mm , Hgb\> 10gm%
- Normal partial thromboplastin time (PTT) and Pro-Thrombin Time (PT)
Exclusion criteria
- Prior treatment with immunomodulatory therapy, immunotherapy, and/or gene vector therapy in the past 3 months.
- Any cytotoxic chemotherapy, RT, or immunotherapy or any investigational drug within 3 weeks of study treatment start.
- Evidence of metastatic disease
- Prostate volume \>50cc
- Prior prostate surgery (hyperthermia, cryotherapy, etc.)
- Prior pelvic radiotherapy
- Prior androgen ablation hormonal therapy (except finasteride if discontinued \> 3 mo. prior to enrollment)
- Patients on corticosteroids or any immunosuppressive drugs.
- History of liver disease, such as cirrhosis or active/chronic hepatitis B or C.
- History of or current alcohol misuse/abuse within the past 12 months.
- Known or suspected allergy or hypersensitivity to any component of the proposed regimen (gene vector/Valacyclovir).
- Inability to swallow food or any condition of the upper gastrointestinal tract that precludes administration of oral medications (Valacyclovir).
- No active malignancy except for non-melanoma skin cancer or in situ cervical cancer or treated cancer from which the patient has been continuously disease free for more than 5 years.
- Presence of active or suspected acute or chronic uncontrolled infection or history of immunocompromise, including a positive HIV test result.
- Patients \< 18 years of age
- Unwilling or unable to comply with the study protocol.
Where
- Houston, Texas
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Apr 6, 2021 · Source of record for eligibility and locations